Brain function and auditory perceptual experiences
Research type
Research Study
Full title
Testing a computational model of the role of excitation/ inhibition (E/I) Balance in perceptual experiences: a combined EEG and MRI study
IRAS ID
357121
Contact name
Oliver Howes
Contact email
Sponsor organisation
King's College London
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
4 years, 10 months, 30 days
Research summary
Auditory hallucinations (falsely perceiving sounds not present in the environment) are a common feature of psychosis. They can affect quality of life and are associated with increased suicide risk(1,2). Currently, antipsychotic medications are used to treat this, but they have side effects and treatment response is insufficient in 40% of patients.(3) To enable more effective treatments to be found, a better understanding of mechanisms behind auditory hallucinations is required. Research has suggested that differences in how brain activity is regulated have been noted in psychosis. Specifically, impairment in the ability to inhibit certain brain signals has been noted in schizophrenia. (4) Impaired functioning of certain nerve cells which create a protein called parvalbumin, which send inhibitory messages to other nerve cells has been noted.(5)
This research aims to understand changes in brain excitation and inhibition in those with auditory hallucinations with schizophrenia spectrum disorder or affective disorder with history of psychosis. We also aim to determine if increasing inhibition restores the balance of excitation and inhibition (E/I balance). To increase inhibition, we will administer a compound named AUT00206 twice daily which has been previously shown to affect the activity of parvalbumin expressing nerve cells and modulate electrical brain signals.(6) Participants will be in the study for a total of up to 4 months, and will receive placebo for 1 month and the compound for 1 month in a crossover design. There will be 13 outpatient visits. We will measure brain electrical activity using a method called EEG, do blood tests, undertake questionnaires to monitor symptoms and do brain imaging (MRI) before and after the compound is taken. We will look at E/I balance using computational analysis. This study will be conducted at NHS and university sites in Manchester and South London, and is being funded by the Wellcome Trust.
REC name
North of Scotland Research Ethics Committee 2
REC reference
25/NS/0100
Date of REC Opinion
21 Oct 2025
REC opinion
Further Information Favourable Opinion